Detecting differences at the cellular level is an ongoing problem which, if successfully addressed, could help solve several prevalent ailments, including cancers and prenatal diseases.
Normal tissue function requires appropriate cell positioning and directional motion. This property, known as chirality, can be altered by genetic and environmental factors, leading to, for example, birth defects and tumor formation.
Current methods to diagnose cancer are based on biomarkers, imaging, and analysis of tissue specimens. In most cases, the findings from one assay (such as imaging) are corroborated by other assays (such as pathological evaluation of biopsy samples).
Chirality is often known as left-right (LR) asymmetry in the development of numerous living organisms, including climbing plants, helices of snail shells, and the human body. Genetic diseases and prenatal exposure to teratogens can cause birth defects in laterality. The LR asymmetry has been studied in animal embryos, which are difficult to control and are not necessarily representative of human condition. Recent studies focused on directional nodal flow driven by primary cilia, pH gradients resulting from asymmetric expression of ion channels, and asymmetric vesicular transport.
The initiation of chirality in development is often first observed in populations of cells of the same type, such as snail embryonic cells at 4-cell and 8-cell stages and mouse cells at embryonic nodes. 2-dimensional (2D) cultures used for determining cell chirality are described in US 2015/0004643.
However, 2D cultures do not fully represent the dynamics of tissue polarization and cell-cell interactions during tissue formation in vivo. Moreover, it is not possible to measure chirality of certain cells with 2D cultures. It would be desirable to have 3-dimensional (3D) cultures to more accurately simulate the complexity of cellular behavior and morphology during natural tissue development.